1. Field of the Invention
The present invention relates to an avian polyomavirus vaccine and to a method of preventing avian polyomavirus infection in Psittaciformes.
2. Background Art
The first acute, generalized infection associated with avian polyomavirus was described in 1980 in young psittacine birds and was called budgerigar fledgling disease (Davis, R. B., et al., "A viral disease of fledgling budgerigars," Avian Dis., 1981, 25:179-183; Bozeman, L. H., et al., "Characterization of a papovavirus isolated from fledgling budgerigars," Avian Dis., 1981, 25:972-980; Bernier, G., et al., "A generalized inclusion body disease in the budgerigar (Melopsittacus undulatus) caused by a papovavirus-like agent," Avian Dis., 1981, 25:1083-1092; Dykstra, M. J., et al., "Investigations of budgerigar fledgling disease virus," Am. J. Vet. Res., 1984, 45:1883-1887; Lehn, H., Muller, H., "Cloning and characterization of budgerigar fledgling disease virus (BFDV), an avian polyomavirus," Virology, 1986, 151:362-370). Since its discovery in 1980, avian polyomavirus has been associated with disease in a number of different species of companion and aviary birds including Budgerigars, caiques, macaws, Amazon parrots, conures, cockatoos, lovebirds, Splendid Parakeets, Pionus Parrots, African Grey Parrots, Eclectus Parrots, Cockatiels, finches and lories (Davis et al., 1981; Bozeman et al., 1981; Bernier et al., 1981; Lehn and Muller, 1986; Jacobson, E. R., et al., "Epornitic of papova-like virus-associated disease in a psittacine nursery," J. Am. Vet. Med. Assoc., 1984, 185:1337-1341; Clubb, S. L., Davis, R. B., "Outbreak of papova-like viral infection in a psittacine nursery-a retrospective view," Proc. Assoc. Avian Vet., Toronto, 1984, 121-129; Graham, D. L., "An update on selected pet bird virus infections," Proc. Assoc. Avian Vet., Toronto, 1984, 267-280; Gaskin, J. M., "Psittacine viral disease: A perspective," J. Zoo. Wildl. Med., 1989, 20:249-264; Johnston, K. M., Riddell, C., "Intranuclear inclusion bodies in finches," Can. Vet. J., 1986, 27:432-434; Marshall, R., "Papova-like virus in a finch aviary," Proc. Assoc. Avian Vet., 1989, 203-207; Schmidt, R. E., et al., "Morphologic identification of papovavirus in a Moluccan cockatoo (Cacatua moluceensis) with neurologic signs," Assoc. Avian Vet. Today, 1987, 1:107-108; Pass, D. A., et al., "A papova-like virus infection of splendid parakeets (Neophema splendida)," Avian Dis., 1987, 31:680-684; Pass, D. A., "A papova-like virus infection of lovebirds (Agapornis sp.)," Aust. Vet. J.; 1985, 82:318-319).
The type of clinical disease in Budgerigars, for example, depends upon the age and condition of the bird when exposure to the virus occurs. Neonates from infected flocks may develop normally for 10-15 days and then suddenly die with no premonitory signs. Other infected hatchlings may develop clinical signs that include abdominal distention, subcutaneous hemorrhage, tremors of the head and neck, ataxia and reduced formation of down and contour feathers (Hirai, K., et al., "Isolation of a papova-like agent from young budgerigars with feather abnormalities," J. Vet. Sci. 46:577-587, 1984; Bernier et al., 1984; Clubb and Davis, 1984; Schmidt et al., 1987; Histopathology Reports #SC90-0637 and #SC90-0638, Schubot Exotic Bird Health Center, Texas A&M University; Vernot, J., personal communication; Dykstra, M. J., Bozeman, L. H., "A light and electron microscopic examination of budgerigar fledgling disease virus in tissue and in cell culture, Avian Pathol. 11:11-18, 1982). Infections have also been associated with decreased hatchability and embryonic death (Hudson, L., Hay, F. C., "Isolation and structure of immunoglobulins," Hudson, L., Hay, F. C. Ed., Practical Immunology, Boston, 1980, 156-202). Mortality rates can be as high as 100% in affected hatchlings. Surviving birds often exhibit dystrophic primary tail feathers, lack of down feathers on the back and abdomen, and lack of filoplumes on the head and neck. Additionally, surviving birds with primary feather abnormalities are usually unable to fly.
In larger psittacine birds, polyomavirus infections may cause peracute death with no premonitory signs, or acute death after development of clinical changes including depression, anorexia, weight loss, delayed crop-emptying, regurgitation, diarrhea, dehydration, subcutaneous hemorrhages, dyspnea, polyuria, and posterior paresis and paralysis (Pass et al., 1987; Johnston and Riddell, 1986; Mathey, W. J., Cho, B. R., "Tremors of nestling budgerigars with budgerigar fledgling disease," Proc. 33rd West. Poult. Dis. Conf., 1984, 102; Woods, L., "Papova-like virus in a purple finch," J. Zoo. Wild. Med., 1989, 218-219; Gaskin, J. M., "The serodiagnosis of psittacine viral infections," Assoc. Avian Vet., Honolulu, 1988, 7-10). Characteristic lesions associated with a polyomavirus infection have been demonstrated in companion birds from the United States (Jacobson et al., 1984; Clubb and Davis, 1984; Graham, 1984), Canada (Gough, J. F., "Outbreaks of budgerigar fledgling disease in three aviaries in Ontario," Can. Vet. J., 1989, 30:672-674, Bernier et al., 1984), Japan (Hirai et al., 1984), Italy (Pascucci, S., et al., "Malattia da virus papova-simile nel papagallino ondulato (Melopsittacus undulatus), Clin. Med. (Milan), 1983, 106:38-41), Hungary (Sztojkov, V., et al., "A hullamous papagaj (Melopsittacus Undulatus) papovavirus okozta megbetegedesenek hazai megallapitasa, Magy Allatorv Lapja 1985, 40:59-63), Germany (Krautwald, M-E, Kaleta, E. F., "Relationship of French moult and early virus induced mortality in nestling budgerigars," Proc. 8th Intl. Cong. World Vet. Poult. Assoc., 1985, 115) and Australia (Pass et al., 1987; Pass, 1985).
Immunodiffusion and virus neutralization techniques have been used to demonstrate anti-polyomavirus antibodies in psittacine birds (Jacobson et al., 1984; Clubb and Davis, 1984; Gaskin, 1989; Davis et al., 1981; Gaskin, 1988; Lynch, J., et al., "Isolation and experimental chicken-embryo-inoculation studies with budgerigar papovavirus," Avian Dis. 1984, 28:1135-1139; Wainwright, P. O., et al., "Serological evaluation of some psittaciformes for budgerigar fledgling disease virus," Avian Dis. 1987, 31:673-676). During epornitics in mixed psittacine bird collections, infected survivors and asymptomatic birds exposed to them have been shown to develop anti-polyomavirus neutralizing antibodies (Jacobson et al., 1984; Clubb and Davis, 1984; Wainwright et al., 1987). Seronegative young adult birds will seroconvert when housed adjacent to seropositive breeding adults, indicating that an antibody response does occur following natural exposure to the virus (Jacobson et al., 1984; Clubb and Davis, 1984; Wainwright et al., 1987; Davis, R. B., "Budgerigar fledgling disease (BFD), 32nd West Poult. Dis. Conf., 1983, 104). However, prior to the present invention it had not been determined whether this antibody response could be induced through vaccination or whether the resulting immunologic response would be protective.
In the past, attempts at producing a vaccine against avian polyomavirus have been unsuccessful. The existence of subclinical infections and chronically infected carrier birds, coupled with a lack of understanding of the epidemiologic and pathophysiologic characteristics of infection have all contributed to the lack of success.
Consequently, avian polyomavirus infections continue to cause high levels of mortality in companion and aviary birds, resulting in psychological distress for clients and financial burdens for aviculturists and retail distributors despite discovery of the virus over 14 years ago. Therefore, there exists a long-felt need in the art for a safe and effective vaccine against avian polyomavirus which is cross-protective against the disease in multiple species of Psittaciformes.
Another problem associated with vaccine failure in Psittaciformes has been the lack of a suitable adjuvant. Two killed oil-adjuvanted herpesvirus (Pacheco's disease virus) vaccines that were conditionally licensed for use in Psittaciformes were found to cause unacceptable reactions in a number of vaccinates, particularly cockatoos (Davis et al., 1981; Bozeman et al., 1981; Bernier et al., 1981; Dykstra et al., 1984). These reactions were characterized by the formation of abscesses (subcutaneous inoculation) or muscle necrosis (IM inoculation). In some Psittaciformes, granulomatous or necrotizing lesions were not noted until several months after vaccination. In other birds, lesions were noted within several weeks of administration of a booster vaccination (Davis et al., 1981; Bozeman et al., 1981; Schmidt et al., 1987). In some cases, deaths have been associated with the use of oil-adjuvanted vaccines.
In general, the advantage of oil-adjuvanted vaccines in comparison to other immunization products is their ability to induce durable immunity when mixed with an inactivated antigen. However, the occurrence of adverse reactions in some Psittaciformes vaccinated with oil-adjuvanted vaccines created the need for an alternative adjuvant for use with inactivated antigens intended for administration in this order of birds (Davis et al., 1981; Bozeman et al., 1981; Schmidt et al., 1987). Therefore, there exists a need in the art for a suitable adjuvant for use in Psittaciformes which augments the immune response yet does not produce an adverse reaction in the vaccinate.